View clinical trials related to Liver Cirrhosis.
Filter by:Chronic liver disease is a major healthcare problem in Hong Kong and worldwide. The diagnosis of liver fibrosis and inflammation in patients with chronic liver disease has important prognostic and therapeutic implications. The current gold standard to evaluate and stage the severity of liver fibrosis and inflammation is based on liver biopsies, which are invasive and impractical for screening and monitoring the disease. The existing non-invasive methods still have significant limitations to meet the challenge. Magnetic resonance effect can be used to obtain the molecular-level information on the biochemical properties of human tissues. The investigators will develop non-invasive quantitative MRI technologies to evaluate and stage liver fibrosis and inflammation. Our approaches are based on the endogenous contrast mechanism and thus do not need to inject an MRI contrast agent. Our approaches can be implemented on a regular MRI scanner and do not need any extra hardware. To enable the technology for routine clinical use, the investigators will develop fully automated post-processing techniques for the proposed MRI acquisition approaches. The investigators will perform multi-center clinical studies in Hong Kong and mainland China to validate our imaging measurements by histopathologic results from liver biopsies on patient cohorts.
Loss of skeletal muscle mass or sarcopenia is the most common and potentially reversible complication in cirrhosis that increases morbidity and mortality before, during and after liver transplantation. No proven treatments exist for the prevention or reversal of sarcopenia in cirrhosis, primarily because the mechanisms responsible for this are unknown. Based on compelling preliminary studies and those of the co investigator, investigators hypothesize that the mechanism of reduced skeletal muscle mass in cirrhosis is due to a myostatin mediated impaired mTOR (mechanistic target of rapamycin) signaling resulting in reduced protein synthesis and increased autophagy. Investigators further postulate that leucine, a direct stimulant of mTOR, will reverse the impaired mTOR phosphorylation in the skeletal muscle of cirrhotics. The consequent increase in protein synthesis reduced autophagy will result in an increase in skeletal muscle mass. Investigators will test these hypotheses by quantifying the response to acute and long term (3 month) administration of hydroxymethyl butyrate (HMB) enriched essential amino acid compared with an isonitrogenous isocaloric non-essential balanced amino acid mixture (does not stimulate protein synthesis) in cirrhotic patients. Fractional protein synthesis rate (FSR) in skeletal muscle, responses of the molecular regulatory pathways of skeletal muscle protein synthesis, and autophagy flux will be quantified in the acute and long term protocols. Tracer studies using L-[D5]-phenylalanine (Phe) as a primed constant infusion (prime 2µmol.kg-1.hr-1; constant 0.05 µmol.kg-1.hr-1) with and L [ring-D2] tyrosine, forearm plethysmography, and sequential skeletal muscle biopsies (total of 3 per study subject) will be used to quantify these outcomes. Anthropometric, clinical and body composition measures will be additional outcome measures for the long term intervention. Expression of regulatory signaling proteins, myostatin, IGF-1 (insulin like growth factor) , phospho-Akt, phospho-AMPK (activated protein kinase), phospho-mTOR and phospho-p70s6k will be quantified by Western immunoblots. Autophagy flux will be measured by quantifying expression of the autophagosome proteins.
Kidney dysfunction is a complex and common event in patients with liver cirrhosis. Although novel treatments have shown some promising results , acute kidney injury remains a major complication of decompensated liver cirrhosis with high morbidity and mortality rates . AKI occurs in up to 19-20% of hospitalized patients with liver cirrhosis and among the most frequent causes are prerenal azotemia (PRA), hepatorenal syndrome and acute tubular necrosis , with prevalence rates estimated around 68%, 25%, and 33%, respectively. The introduction and widespread use of diagnostic criteria of AKI in the area of cirrhosis has contributed to an increased awareness and earlier detection of AKI. However, some important problems remain. One of the main issues is the differential diagnosis of AKI, particularly between acute tubular necrosis (ATN) and hepatorenal syndrome (HRS-AKI). This is important because treatment is different; renal replacement therapy (RRT) is used for the former, and vasoconstrictors and albumin are used for the latter.
The main purpose of this study is to evaluate the safety and tolerance of umbilical cord mesenchymal stem cells (UCMSCs) in patients with decompensated alcoholic cirrhosis, and to provide dose basis for subsequent clinical study design. We will also explore the possible mechanism of UCMSCs in the treatment of decompensated alcoholic cirrhosis (DAC).
Liver fibrosis is the main feature in early chronic liver diseases. If identified early, liver fibrosis is reversible. The current gold standard for diagnosing liver fibrosis is invasive liver biopsy. Existing non-invasive methods still have significant limitations. T1rho imaging is a promising non-invasive technology evaluating liver fibrosis. It does not require exogenous contrast agent or extra hardware. However, it remains challenging to perform T1rho measurements of the liver. The rich blood signal in the liver introduces quantification errors of liver parenchyma. The existing black blood MRI technologies are based on Cartesian FSE acquisitions, which are not optimal for liver imaging. The residual blood signal is often observed which confounds the measurement. Current T1rho measurement of the liver is mostly performed in two-dimension. 3D coverage of liver is desirable. However, 3D T1rho imaging of liver suffers from long scan time due to increased spatial coverage, reduced scan time efficiency from motion compensation, and high specific absorption rate (SAR). The investigators aim to overcome these challenges by developing 3D T1rho imaging technologies based on magnetization prepared spiral FSE acquisition. Compared to Cartesian FSE, Spiral FSE traverses k-space more efficiently per unit of time, and has reduced SAR due to significantly decreased number of radiofrequency pulses in the echo trains. Spiral acquisition has zero gradient moment at the kspace center, which substantially reduces its sensitivity to respiratory motion. The residual motion manifests as benign incoherent artifacts in the image domain rather than detrimental structured artifacts. Differently to Cartesian FSE, Spiral FSE provides flexibility to design and optimize flow-sensitizing gradients throughout the echo trains to achieve superior suppression of blood signal. The investigators will evaluate the proposed pulse sequences in both healthy controls and patients with liver fibrosis. This project will provide new black blood imaging technologies and a 3D diagnostic tool for early detection of liver fibrosis. This will improve clinical outcomes for patients with chronic liver disease, and provide a springboard for further development of MRI technology for other purposes.
Liver T1rho is elevated in response to accumulation of extracellular matrix proteins during fibrosis. The presence of hepatic iron overload; however, can shorten the T1rho value. With proper correction, we can remove this confounding factor and improve the reliability of T1rho for early diagnosis of liver fibrosis. Patients with early-stage liver fibrosis confirmed by biopsy will be recruited at the Prince of Wales Hospital (Hong Kong). Thirty patients and twenty healthy volunteers will be recruited. The liver iron content will be measured using the established T2* MRI relaxometry. Breathhold black blood T1rho relaxometry will be used to collect T1rho data. The measured T1rho will be retrospectively corrected to remove the shortening effect caused by iron. We will use ANOVA to compare the measurement with and without fibrosis. We will use Pearson correlations between the disease state and the imaging measurements, and ROC analysis to determine the diagnostic value of the proposed method.
Chronic hepatitis B (CHB) affects 257million individuals worldwide. In 2017, it caused around 39.7 million cases of cirrhosis and 0.4 million cirrhosis-related deaths in 2017. However, there is no specific treatment for liver fibrosis/cirrhosis. Although nucleos(t)ide analogues (NAs) profoundly suppress viral replication, fibrosis/cirrhosis progression can still occur in NA-treated patients. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are antidiabetic drugs that may prevent fibrosis/cirrhosis progression by reducing hepatic steatosis/inflammation, dampening renin-angiotensin aldosterone system (RAAS) activation, and reducing fluid retention, effects of which are independent of glycemic control. Clinical studies in diabetic patients show SGLT2 inhibitors reduce hepatis steatosis/inflammation, regress ascites (a cirrhotic complication), and improve liver function parameters and survival prognosis in terms of model for end-stage liver disease (MELD) score. There are currently no randomized controlled trials (RCTs) on role of SGLT2 inhibitors in preventing fibrosis/cirrhosis progression in CHB patients. Magnetic resonance elastography (MRE) and transient elastography (TE) are non-invasive techniques for liver stiffness measurement (LSM), although MRE is more accurate than TE. The investigators propose a double-blind, randomized, placebo-controlled trial to compare effect of empagliflozin (an SGLT2 inhibitor) with placebo (1:1 ratio) in preventing fibrosis progression in both diabetic and non-diabetic NA-treated CHB patients with significant/advanced fibrosis or compensated cirrhosis. 108 patients will be randomly sampled from our pre-existing TE database. Empagliflozin 10mg daily will be given to treatment arm. Placebo pills will be manufactured identical in appearance to empagliflozin. Subjects will receive active or placebo pills for three years, and undergo clinical, anthropometric and laboratory assessments (at baseline, weeks 8, 16, and every 4 months thereafter). They will undergo LSM by TE at baseline, end of first, second and third year, and by MRE at baseline and end of third year. Primary outcome is difference in change to liver stiffness (measured by MRE) from baseline between the two groups at the end of third year. The study results will determine whether SGLT2 inhibitors can prevent hepatic fibrosis/cirrhosis progression in NA-treated CHB patients.
This project aims to test a behavioral intervention in patients with liver cirrhosis and chronic pain and teach self pain-management skills.
Hepatic encephalopathy is the most common complication after TIPS, and hepatic encephalopathy occurs in almost all portosystemic shunts. For patients with severe upper gastrointestinal bleeding or refractory ascites in the decompensated chronic hepatitis B, transjugular intrahepatic portosystemic shunt (TIPS) is a very effective treatment. However, due to the severe complications such as hepatic encephalopathy after TIPS, the clinical application of TIPS is limited. Literature studies have shown that the incidence of encephalopathy after TIPS is about 35%. TIPS reduces the portal vena blood flow into the liver by establishing a new channel. But at the same time, the toxic substances from the gastrointestinal tract and other organs do not enter the liver to detoxify, and are more likely to enter the brain, leading to hepatic encephalopathy. Moreover, studies have found that the liver and the intestine originate from the same germ layer and are closely related to each other in anatomy and function. There are a large number of microorganisms living in the intestinal tract. Normally, the intestinal tract, as the first defense of the human body, can effectively prevent bacteria and their products from entering the bloodstream. In cirrhosis and portal hypertension, blood return disorder causes intestinal damage. A series of microbes and product endotoxins such as gram-negative bacteria will enter the blood through the injury, and the toxins in the peripheral blood will enter the brain and cause hepatic encephalopathy happened. The research team's early treatment plan with integrated traditional Chinese and Western medicine proved that it greatly reduced the incidence of hepatic encephalopathy after TIPS. And improve the clinical symptoms and signs of patients with liver cirrhosis, and improve the quality of life and survival of patients.
In this project, we plan to evaluate whether a new, rotational thromboelastometry-guided algorithm (ROTEM) to guide hemostatic resuscitation decreases the use of allogeneic blood products, the total amount of bleeding, transfusion related side effects, thromboembolic complications and costs. Its effect on each patient's post-operative hemostatic profile is also measured. We plan to enroll 140 patients having ACLF with variceal bleeding randomized into two groups: one will be treated conventionally using clinical judgement and standard coagulation tests such as prothrombin time, platelet count, etc. the other treated using a ROTEM-based algorithm. They will be followed for development of rebleeding, complications of transfusion and any signs of infection after hospitalization